Depression relapse

Lamotrigine is effective for the maintenance treatment of bipolar disorder. It is more effective for depression relapse prevention than for mania relapse. Its primary limitation as an acute treatment is the time required for titration to an effective dosage. In addition to maintenance monotherapy, it is sometimes used in combination with lithium or divalproex, although combination with divalproex increases the risk of rash, and lamotrigine dosage adjustment is required.37... 

Duration of antidepressant therapy is also an unsettled question. It may be possible in some patients to prevent depressive relapse with a mood-stabilizing drug without maintenance antidepressant therapy following acute treatment with an antidepressant. If so, the risk of a mood switch with continued antidepressant therapy would be reduced. 

Neuropsychiatric events Life-threatening or fatal neuropsychiatric events, including suicide, suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior have occurred in patients with and without a previous psychiatric disorder during peginterferon alfa-2b treatment and follow-up. Psychoses, hallucinations, bipolar disorders, and mania have been observed in patients treated with alpha interferons. 

Rouillon F, Serrurier D, Miller H, et al Prophylactic efficacy of maprotiline on unipolar depression relapse. J Chn Psychiatry 52 423-431, 1991 Rowan MJ, Cullen WK, Moulton B Buspirone impairment of performance of passive avoidance and spatial learning tasks in the rat. Psychopharmacology 100 393-398,... 

Given their design differences, no direct comparison can be made between the relative relapse efficacy of SSRIs, venlafaxine, and nefazodone. The bottom line, however, is that both designs demonstrated that maintenance therapy for up to 1 year is important in reducing the risk of a depressive relapse after an initial response. 

Further, some of the studies did not report the number of manic versus depressive relapses. One exception is Coppen et al. ( 176, 177), who reported the mean affect morbidity score of patients receiving placebo (mean SD, 0.33 0.05) or lithium (0.09 0.05) for the manic phase, as well as placebo (0.31 0.06) or lithium (0.07 0.03) for the depressive phase. Thus, this study found very similar prophylactic effects. Baastrup and associates ( 6) reported a comparable number of manic and depressed phase relapses in their bipolar patients. In 22 bipolar patients, 12 relapsed six into a manic phase, five into a depressed phase, and one into a mixed phase. By contrast, Prien et al. (182) and Cundall et al. (178) found that lithium had a greater effect in preventing the manic than the depressed phase of bipolar disorder. Overall, lithium was effective in preventing both phases of a bipolar disorder. 

Two terms beginning with the letter R are used to describe worsening in a patient with depression, relapse and recurrence. If a patient worsens before there is a complete remission or before the remission has turned into a recovery, it is called a relapse (Fig. 5—4). However, if a patient worsens a few months after complete recovery, it is called a recurrence. The features that predict relapse with greatest accuracy are (1) multiple prior episodes (2) severe episodes (3) long-lasting episodes (4) episodes with bipolar or psychotic features and (5) incomplete recovery between two consecutive episodes, also called poor interepisode recovery (Table 5—11). 

Withdrawal symptoms in the 2 weeks after sudden discontinuation of citalopram have been examined in a double-blind, placebo-controlled study (24). Withdrawal symptoms were overall mild, but neurological and psychiatric disturbances were 2-3 times as common in patients randomized to placebo than in those randomized to continue with citalopram. The authors pointed out that withdrawal symptoms were particularly common in patients who were randomized to placebo who also had depressive relapses. This shows the difficulty of disentangling the effects of depressive relapse from those of pure treatment withdrawal. However, it is also possible that acute withdrawal of medication induces an abnormal neu-robiological state, in which both depression and abstinence symptoms are more likely to occur. It would be wise to warn patients about the possible effects of missing doses of the shorter-acting SSRIs. 

In a study of the use of phenelzine in continuation therapy after recovery from an acute episode of depression, relapse rates were higher in patients subjected to tapered withdrawal than in those who continued taking the therapeutic dose (8). 

In a review of five randomized controlled trials of prevention of relapse in 770 patients with bipolar affective disorder, lithium has been compared with placebo (98). Lithium was more effective than placebo in preventing all relapses and manic relapses, but the effect on depressive relapses was not as impressive and was termed equivocal by the authors. This is not particularly new information, although several of the studies that were included in this meta-analysis were more recent and the analysis was presented as odds ratios rather than episode frequency. 

Monitroing serum lithium concentrations has been reviewed (733). Lithium concentrations are important predictors of outcome, but can also be associated with the type of outcome. Low lithium concentrations (< 0.6 mmol/1) are associated with a low likelihood of depressive relapse (12%), while higher concentrations (> 0.8 mmol/1) are associated with a higher likelihood of depressive relapse (64%) (734). This has been interpreted as showing that low concentrations, rather than higher concentrations, of lithium are more effective in... 

Following remission of manic symptoms in 37 patients who had taken perphenazine and a mood stabilizer (lithium, carbamazepine, or valproate), treatment was randomly assigned double-blind to perphenazine or placebo for 6 months, while continuing the mood stabilizer (1). Those who took perphenazine had worse outcomes than those who took placebo, in that they were more likely to have a shorter time to a depressive relapse, were more likely to discontinue treatment, or were more likely to have depression or extrapyramidal symptoms. The authors tentatively concluded that perphenazine may not be beneficial in maintenance treatment for bipolar I patients. 

Berman RM, Narasimhan M, Miller HL, Anand A, Cappiello A, Oren DA, Heninger GR, Charney DS. Transient depressive relapse induced by catecholamine depletion potential phenotypic vulnerability marker Arch Gen Psychiatry 1999 56(5) 395-403. 

Regulation of mood, sleep, and aggression have all been shown to involve the serotoninergic system (17-19), and most antidepressant drugs currently being used inhibit 5-HT reuptake and/or act on 5-HT receptors (of which there are several subtypes). 5-HT is produced centrally from the amino acid tryptophan, and depressed mood can be induced experimentally by acute tryptophan depletion in healthy individuals. This effect is accentuated in those with a family history of depression (18-21). Similarly, depressive relapse can be initiated in individuals treated with MAO inhibitors or selective serotonin reuptake (SSRI) inhibitors by depleting tryptophan (22, 23). 

Delgado et al.20 studied the behavioral effects of rapid (24 h) tryptophan depletion in patients in antidepressant-induced remission. Patients receiving antidepressants leading to remission were then given a tryptophan-free amino acid drink, and they experienced a depressive relapse. Free plasma tryptophan level was negatively correlated with the depression score during acute tryptophan depletion. A number of other studies on the effects of tryptophan depletion on relapse of depression after treatment confirmed the previous findings.37 11... 

Depressive relapses less effective, but most evidence for lithium... 

Acute mania often needs admission hypomania can often be managed in the community - see Ch.54 (mania) and Ch.62 (relapse). For depressive relapse, see What if... ... 

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